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Please login or sign up for a free trial to access the full content. Deprotonative Construction of a Carbon-Carbon Single Bond under an SN2 or SN2′ Mechanism

DOI: 10.1055/sos-SD-134-00125

Yamazaki, T.Science of Synthesis Knowledge Updates, (20172299.

As described in Section (Scheme 15), fluorobis(phenylsulfonyl)methane is a versatile building block for the construction of a variety of fluorine-containing compounds by taking advantage of the easy removal of the phenylsulfonyl moiety. In the first reaction shown in Scheme 19, the hydroquinidine (anthraquinone-1,4-diyl) diether (52) undergoes SN2′-type reaction with acceptor acrylates, prepared by Morita–Baylis–Hillman reactions, followed by further SN2′-type reaction of fluorobis(phenylsulfonyl)methane in its anionic form with the formed intermediates. This allows formation of net SN2-type products 54 in high chemical and optical yields.[‌39‌] To improve the overall outcome of this process further, investigation into finding appropriate additives has led to the conclusion that the introduction of Lewis acids such as iron(II) chloride and titanium(IV) isopropoxide is effective to some extent owing to the formation of a bidentate chelate with fluorobis(phenylsulfonyl)methane, which plays an important role in locking the conformation; this is supported by a downfield shift in the signal for the methine proton in the 1H NMR spectrum. An analogous, independent study employing the exact same reactants and base catalyst, but with the use of mesitylene as the solvent and a reaction temperature of 30 °C, reports the formation of products 54 in yields of 71 to 99% with 90–97% ee.[‌40‌] Exchange of the solvent to toluene has also been shown to be an easy method to improve the optical purity of 54 to almost perfect.

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Meeeee 88 Meeeeeeeeeeeeee Meeeeeeeeeee ee e Meeeeeeee(eeeeeeeeeeeeee)eeeeee Meeee[‌88‌‌88‌]

Meeeeeeeeee 88

M8 Meeeeeee ee (%) Meeee (%) Mee
Me 88 88 [‌88‌]
Me 88 88e [‌88‌]
Me >88.8 88e [‌88‌]
8-MeM8M8 88 88 [‌88‌]
8-MeM8M8 MeMe8 88 88 [‌88‌]
8-MeM8M8 Me(MeMe)8 88 88 [‌88‌]
8-MeM8M8 88 88 [‌88‌]
8-MeM8M8 MeMe8 88 88 [‌88‌]
8-MeM8M8 Me(MeMe)8 88 88 [‌88‌]
8-MeM8M8 88 88 [‌88‌]
8-MeM8M8 MeMe8 88 88 [‌88‌]
8-MeM8M8 Me(MeMe)8 88 88 [‌88‌]
8-Mee 88 88 [‌88‌]
8-Mee MeMe8 88 88 [‌88‌]
8-Mee Me(MeMe)8 88 88 [‌88‌]
8-M8MM8M8 88 88 [‌88‌]
8-M8MM8M8 MeMe8 88 88 [‌88‌]
8-M8MM8M8 Me(MeMe)8 88 88 [‌88‌]

e Meeeeeee eee eeeeeeeee ee eeeeeeeeee ee 88 °M eee 88 e.

e Meeeeeee eee eeeeeeeee ee eeeeeee ee 88 °M eee 88 e.

M8 ee (%) Meeee (%) Mee
Me 88 88 [‌88‌]
8-MeMM8M8 88 88 [‌88‌]
8-MeM8M8 88 88 [‌88‌]
8-eeeeeeee 88 88 [‌88‌]
8-eMeM8M8 88 88 [‌88‌]

M eeeeeee eeeeeee eeeeeeeeeeee eeeeeeee eee eee 8-eeeeeeeeeee 8-eeeeeeeee-8,8-eeeee eeeeee eeeeeeee eeee eee eee ee eee eee(η8-eeeee)eeeeeeeeeeeeeeeeeee(MM) eee 8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeee (88) eeeeeeee eeeeee,[‌88‌] eeeee eeeeee eeeeee eee eeeeeeeeee ee eee eeeeeeeeee eeee eeeeeeeeeeeee eeeeeee 88 ee e eeeeee ee eee eeeeeeee eeeeeeeee ee eee eeee-eeeeeeee eeeeeeee eeeeee eeee (Meeeee 88).

Meeeee 88 Meeeeeee ee Meeeeeeee(eeeeeeeeeeeeee)eeeeeee eeee 8-Meeeeeeee-8,8-eeeeee[‌88‌]

Meeeeeeeeee 88

M8 M8 M8 Meeee (%) Mee
Me M M 88 [‌88‌]
e-Me M M 88 [‌88‌]
(MM8)8Me M M 88 [‌88‌]
8-MeMM8M8 M M 88 [‌88‌]
8-M8MM8M8 M M 88 [‌88‌]
Me Me Me 88 [‌88‌]
Me Me M 88 [‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeee (8M)-8-Meeeee-8-eeeeeeeee-8-eeeeee-8,8-eee(eeeeeeeeeeeeee)eeeeeeeee [(M)-88, M8 = Me]; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eee Meeeee–Meeeeee eeeeeeeee (M8 = Me; 88.8 ee, 8.888 eeee), (MeMM8)8MMM (88.8 ee, 8.888 eeee), eee (MMMM)8MMM (88; 8.8 ee, 8.888 eeee) eee eeeeeeeee ee eee (eeeeeeeeeeeeeee)eeeeeee (8.8 eM). Mee eeeeeee eee eeeeee ee 88 °M eee, eeeee 8 e, eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MM8Me8 8:8) ee eeee eee eeeee eeeeeeee ee e eeeee eeeee; eeeee: 88.8 ee (88%); 88M MMM (MMMe8, 888 MMe, δ): −888.8 (e, M = 88.8 Me).

(M,M)-8-Meeeee-8,8-eee(8-eeeeeeeeeeeeee)-8,8-eee(eeeeeeeeeeeeee)eee-8-eee [(M)-88, M8 = 8-eMeM8M8]; Meeeeee Meeeeeeee:[‌88‌]

M eeee ee (M)-8,8-eee(8-eeeeeeeeeeeeee)eeee-8-eeee eeeeeee (888 ee, 8.888 eeee), (M)-eMe-MMMM (88; 88.8 ee, 8.888 eeee, 8 eee%), eee Me88-MM8MM=MM8)8Me8 (8.8 ee, 8.888 eeee, 8.8 eee%) ee MM8Me8 (8.8 eM) eee eeeeeee ee ee eee 8 eee. (MeMM8)8MMM (888 ee, 8.888 eeee) eee Me8MM8 (888 ee, 8.888 eeee) eeee eeee eeeee ee 8 °M. Mee eeeeeeeee eeee eee eeeeeee ee 8 °M eee 8 e, ee eeeee eeeee eee eeeeeee eee eeeeeeeeee eeeeeeee (MMM eeeeeeee). Mee eeeeeee eee eeeeee eeee eee. ee MM8Me eee eeeeeeeee eeee MM8Me8; eee eeeeeee eeeee eee eeee eeeee (Me8MM8). Meeee eeeeeeeeeee ee eee eeeeeee eeeee eeeeeee eeeeeeee, eee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee) ee eeee eee eeeee eeeeeeee ee e eeeeeeeee eeeee; eeeee: 888 ee (88%); 88% ee; 88M MMM (MMMe8, 888 MMe, δ): −888.8 (e, M = 88.8 Me).

8-Meeeeeeeeee 8-Meeeee-8,8-eee(eeeeeeeeeeeeee)eeeee-8,8-eeeeee 88; Meeeeee Meeeeeeee:[‌88‌]

Mee eeeeeeeeee (8.88 eeee) eee eeeee ee eeeeeee ee e eeeeeee ee Me88-MM8MM=MM8)8Me8 (8.8 ee, 8.8 µeee), 8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeee (88; 8.8 ee, 88 µeee), (MeMM8)8MMM (88 ee, 8.88 eeee), eee e-MeMM (88 ee, 8.88 eeee) ee MM8Me8 (8.8 eM) eeeee ee eeeeeeeeee ee M8. Meeee eeeee eeeeeee eee 88 e ee 88 °M, eee eeeeeee eee eeeeeee eeee Me8M eee eeeeeeee eeeeeee e eeeee eee ee eeeeee eee ee eeeeee eee eeeeeeeeeeee eeeeeeeee eeeee. Mee eeeeee eee eee eee eeeeee eeee e eeeee eeeeee ee Me8M (8 ×), eee eee eeeeeeee eeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee) ee eeee eee eeeee eeeeeeee. Meeeeeeeeeeeee MMM eeee eee 88 (M8 = e-Me; M8 = M8 = M): 88M MMM (MMMe8, 888 MMe, δ): −888.8 (ee, M = 88.8, 88.8 Me).